IARS2 (isoleucyl-tRNA synthetase 2, mitochondrial)

Gene

• Entrez ID: 55699
• Gene name: Isoleucyl-tRNA synthetase 2, mitochondrial
• Gene symbol: IARS2
• Synonyms (NCBI Gene): CAGSSS, ILERS
• Chromosome: 1
• Chromosome location: 1q41
• Summary: Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAS, aminoacyl-tRNA synthetases are thought to be among the first prot

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs143722284	G>A	Pathogenic, likely-benign	Coding sequence variant, missense variant
rs146618526	G>A,T	Pathogenic	Missense variant, coding sequence variant
rs151241066	G>A	Pathogenic	Missense variant, coding sequence variant
rs373436822	G>A	Pathogenic, uncertain-significance	Coding sequence variant, stop gained
rs587783070	C>T	Pathogenic	Coding sequence variant, missense variant
rs773732328	C>A,G,T	Likely-pathogenic	Coding sequence variant, synonymous variant, stop gained, missense variant
rs1287308680	C>A,T	Likely-pathogenic	Stop gained, coding sequence variant, missense variant
rs1571845061	T>C	Pathogenic	Coding sequence variant, missense variant
rs1571863769	A>G	Pathogenic	Coding sequence variant, missense variant
rs1571865562	C>T	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT052088	hsa-let-7b-5p	CLASH	23622248
MIRT049747	hsa-miR-92a-3p	CLASH	23622248
MIRT048072	hsa-miR-197-3p	CLASH	23622248
MIRT040636	hsa-miR-92b-3p	CLASH	23622248
MIRT1058046	hsa-miR-3180-5p	CLIP-seq
MIRT1058047	hsa-miR-376a	CLIP-seq
MIRT1058048	hsa-miR-376b	CLIP-seq
MIRT1058049	hsa-miR-487a	CLIP-seq
MIRT1058050	hsa-miR-520a-5p	CLIP-seq
MIRT1058051	hsa-miR-525-5p	CLIP-seq
MIRT1058052	hsa-miR-532-5p	CLIP-seq
MIRT2013337	hsa-miR-1278	CLIP-seq
MIRT2013338	hsa-miR-3682-5p	CLIP-seq
MIRT2013339	hsa-miR-3920	CLIP-seq
MIRT2013340	hsa-miR-4427	CLIP-seq
MIRT2013341	hsa-miR-4659a-3p	CLIP-seq
MIRT2013342	hsa-miR-4659b-3p	CLIP-seq
MIRT2013343	hsa-miR-4680-3p	CLIP-seq
MIRT2013344	hsa-miR-4700-3p	CLIP-seq
MIRT2013345	hsa-miR-4712-5p	CLIP-seq
MIRT2013346	hsa-miR-4762-3p	CLIP-seq
MIRT2013347	hsa-miR-4778-3p	CLIP-seq
MIRT2013348	hsa-miR-5095	CLIP-seq
MIRT2013349	hsa-miR-770-5p	CLIP-seq
MIRT2013337	hsa-miR-1278	CLIP-seq
MIRT2245559	hsa-miR-2053	CLIP-seq
MIRT2245560	hsa-miR-3160-3p	CLIP-seq
MIRT2013339	hsa-miR-3920	CLIP-seq
MIRT2245561	hsa-miR-4433	CLIP-seq
MIRT2245562	hsa-miR-4459	CLIP-seq
MIRT2245563	hsa-miR-4476	CLIP-seq
MIRT2245564	hsa-miR-4487	CLIP-seq
MIRT2245565	hsa-miR-4676-5p	CLIP-seq
MIRT2245566	hsa-miR-4691-5p	CLIP-seq
MIRT2013344	hsa-miR-4700-3p	CLIP-seq
MIRT2013345	hsa-miR-4712-5p	CLIP-seq
MIRT2013346	hsa-miR-4762-3p	CLIP-seq
MIRT2245567	hsa-miR-4768-3p	CLIP-seq
MIRT2245568	hsa-miR-4779	CLIP-seq
MIRT2013348	hsa-miR-5095	CLIP-seq
MIRT2245569	hsa-miR-558	CLIP-seq
MIRT2245570	hsa-miR-569	CLIP-seq
MIRT2245571	hsa-miR-575	CLIP-seq
MIRT2013349	hsa-miR-770-5p	CLIP-seq
MIRT2548817	hsa-miR-3119	CLIP-seq
MIRT2548818	hsa-miR-3124-3p	CLIP-seq
MIRT2548819	hsa-miR-3160-5p	CLIP-seq
MIRT2548820	hsa-miR-3163	CLIP-seq
MIRT2548821	hsa-miR-337-3p	CLIP-seq
MIRT2548822	hsa-miR-340	CLIP-seq
MIRT2548823	hsa-miR-3685	CLIP-seq
MIRT2548824	hsa-miR-384	CLIP-seq
MIRT2245566	hsa-miR-4691-5p	CLIP-seq
MIRT2548825	hsa-miR-4699-3p	CLIP-seq
MIRT2548826	hsa-miR-4797-5p	CLIP-seq
MIRT2548817	hsa-miR-3119	CLIP-seq
MIRT2548818	hsa-miR-3124-3p	CLIP-seq
MIRT2548819	hsa-miR-3160-5p	CLIP-seq
MIRT2548821	hsa-miR-337-3p	CLIP-seq
MIRT2548823	hsa-miR-3685	CLIP-seq
MIRT2548824	hsa-miR-384	CLIP-seq
MIRT2245566	hsa-miR-4691-5p	CLIP-seq
MIRT2548825	hsa-miR-4699-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000049	Function	TRNA binding	IEA
GO:0000166	Function	Nucleotide binding	IEA
GO:0002161	Function	Aminoacyl-tRNA deacylase activity	IEA
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004822	Function	Isoleucine-tRNA ligase activity	IBA
GO:0004822	Function	Isoleucine-tRNA ligase activity	IEA
GO:0004822	Function	Isoleucine-tRNA ligase activity	TAS
GO:0005524	Function	ATP binding	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006412	Process	Translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	TAS
GO:0006428	Process	Isoleucyl-tRNA aminoacylation	IBA
GO:0006428	Process	Isoleucyl-tRNA aminoacylation	IEA
GO:0016874	Function	Ligase activity	IEA
GO:0032543	Process	Mitochondrial translation	IBA
GO:0106074	Process	Aminoacyl-tRNA metabolism involved in translational fidelity	IEA

Other IDs

• MIM: 612801
• HGNC: 29685
• e!Ensembl: ENSG00000067704

Protein

• UniProt ID: Q9NSE4
• Protein name: Isoleucine--tRNA ligase, mitochondrial (EC 6.1.1.5) (Isoleucyl-tRNA synthetase) (IleRS)
• Protein function: Aminoacyl-tRNA synthetase that catalyzes the specific attachment of isoleucine to its cognate tRNA (tRNA(Ile)).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00133	tRNA-synt_1	87 → 712	tRNA synthetases class I (I, L, M and V)	Family
  PF08264	Anticodon_1	756 → 921	Anticodon-binding domain of tRNA ligase	Domain
  PF06827	zf-FPG_IleRS	984 → 1008	Zinc finger found in FPG and IleRS	Domain

• Sequence:

  MRWGLRPRGPGAAALATARSLWGTPRLPCSPGWQGATKRLLVRSVSGASNHQPNSNSGRY
  RDTVLLPQTSFPMKLLGRQQPDTELEIQQKCGFSELYSWQRERKVKTEFCLHDGPPYANG
  DPHVGHALNKILKDIANRFHMMNGSKIHFVPGWDCHGLPIEIKVLSELGREAQNLSAMEI
  RKKARSFAKAAIEKQKSAFIRWGIMADWNNCYYTFDGKYEAKQLRTFYQMYDKGLVYRSY
  KPVFWSPSSRTALAEAELEYNPEHVSRSIYVKFPLLKPSPKLASLIDGSSPVSILVWTTQ
  PWTIPANEAVCYMPESKYAVVKCSKSGDLYVLAADKVASVASTLETTFETISTLSGVDLE
  NGTCSHPLIPDKASPLLPANHVTMAKGTGLVHTAPAHGMEDYGVASQHNLPMDCLVDEDG
  VFTDVAGPELQNKAVLEEGTDVVIKMLQTAKNLLKEEKLVHSYPYDWRTKKPVVIRASKQ
  WFINITDIKTAAKELLKKVKFIPGSALNGMVEMMDRRPYWCISRQRVWGVPIPVFHHKTK
  DEYLINSQTTEHIVKLVEQHGSDIWWTLPPEQLLPKEVLSEVGGPDALEYVPGQDILDIW
  FDSGTSWSYVLPGPDQRADLYLEGKDQLGGWFQSSLLTSVAARKRAPYKTVIVHGFTLGE
  KGEKMSKSLGNVIHPDVVVNGGQDQSKEPPYGADVLRWWVADSNVFTEVAIGPSVLNAAR
  DDISKLRNTLRFLLGNVADFNPETDSIPVNDMYVIDQYMLHLLQDLANKITELYKQYDFG
  KVVRLLRTFYTRELSNFYFSIIKDRLYCEKENDPKRRSCQTALVEILDVIVRSFAPILPH
  LAEEVFQHIPYIKEPKSVFRTGWISTSSIWKKPGLEEAVESACAMRDSFLGSIPGKNAAE
  YKVITVIEPGLLFEIIEMLQSEETSSTSQLNELMMASESTLLAQEPREMTADVIELKGKF
  LINLEGGDIREESSYKVIVMPTTKEKCPRCWKYTAESSDTLCPRCAEVVSGK

• Sequence length: 1012

Pathways

KEGG:

Aminoacyl-tRNA biosynthesis

Reactome:

Mitochondrial tRNA aminoacylation

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome	Likely pathogenic; Pathogenic	rs151241066, rs1571845061, rs146618526, rs1571865562, rs1571863769	RCV000791254 RCV000791255 RCV000791256 RCV000791257 RCV000791258
Leigh syndrome	Likely pathogenic; Pathogenic	rs754577516	RCV003110149

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Benign	rs75519000	RCV005896292
Cataract	Conflicting classifications of pathogenicity	rs587783070	RCV000144718
Cervical cancer	Benign	rs78770848	RCV005896317
Cholangiocarcinoma	Benign	rs75519000	RCV005896297
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign	rs78770848	RCV005896326
Colon adenocarcinoma	Benign; Likely benign	rs78770848, rs142067804	RCV005896315 RCV005907690
Developmental cataract	Uncertain significance	rs2102820352	RCV001775026
Familial cancer of breast	Benign; Likely benign	rs75519000, rs142067804	RCV005896291 RCV005907689
Familial pancreatic carcinoma	Benign	rs78770848	RCV005896319
growth hormone deficiency with short stature	Conflicting classifications of pathogenicity	rs587783070	RCV000144718
Hepatocellular carcinoma	Uncertain significance; Benign	rs151085900, rs75519000	RCV005932122 RCV005896293
IARS2-related disorder	Benign; Likely benign; Uncertain significance	rs138462058, rs149036509, rs775353772, rs1436717034, rs189498035, rs574253271, rs377623873, rs78770848, rs2577154, rs78836180, rs116823205, rs772530946, rs199601961	RCV003931227 RCV003913459 RCV003906496 RCV003951973 RCV003957002 RCV003962328 RCV003932660 RCV003972591 RCV003970150 RCV003972588 RCV003922747 RCV003903179 RCV003960478
Lymphoma	Benign	rs78770848, rs11800305	RCV005896321 RCV005896568
Malignant lymphoma, large B-cell, diffuse	Benign	rs75519000	RCV005896295
Malignant tumor of urinary bladder	Benign; Likely benign	rs142067804	RCV005907691
Nonpapillary renal cell carcinoma	Benign	rs78770848	RCV005896316
Ovarian cancer	Benign	rs78770848	RCV005896318
Ovarian serous cystadenocarcinoma	Benign; Likely benign	rs142067804	RCV005907692
partial sensorineural deafness	Conflicting classifications of pathogenicity	rs587783070	RCV000144718
Peripheral neuropathy	Conflicting classifications of pathogenicity	rs587783070	RCV000144718
Sarcoma	Benign	rs78770848	RCV005896320
Thymoma	Benign	rs78770848	RCV005896323
Thyroid cancer, nonmedullary, 1	Benign; Likely benign	rs78770848, rs142067804	RCV005896324 RCV005907694
Uterine carcinosarcoma	Benign; Likely benign	rs78770848, rs75519000, rs142067804	RCV005896322 RCV005896296 RCV005907693
Uterine corpus endometrial carcinoma	Benign	rs78770848	RCV005896325
Uveal melanoma	Benign	rs75519000	RCV005896294

Associations from Text Mining
Disease Name	Relationship Type	References
Anemia Sideroblastic	Associate	33327715
Cataract	Associate	29914532, 30419932
Colorectal Neoplasms	Associate	26722399
Congenital Abnormalities	Associate	30419932
Dwarfism Pituitary	Associate	30419932
Hearing Loss Sensorineural	Associate	30419932
HEM dysplasia	Associate	30419932
Hereditary Sensory and Autonomic Neuropathies	Associate	30419932
Hirschsprung Disease	Associate	28006787
Leukemia	Associate	30832756
Leukemia Myeloid Acute	Associate	30832756
Mitochondrial Diseases	Associate	30419932
Neurologic Manifestations	Associate	30419932
Polyneuropathies	Associate	30419932
Spasms Infantile	Associate	30419932